EFFICACY OF ROFLUMILAST IN THE TREATMENT OF FLEXURAL AND/OR GENITAL PSORIASIS: A RANDOMIZED CONTROLLED TRIAL.

Phase 2Not Yet RecruitingNCT07543640

Eman Raafat Said56 enrolled

Overview

Psoriasis affecting sensitive anatomical regions, such as the skin folds (flexural or inverse psoriasis) and genitalia, presents unique therapeutic challenges. These manifestations often result in a disproportionately high burden of disease, causing significant physical discomfort and a profound negative impact on a patient's quality of life and sexual health. While topical creams are the standard first-line treatment, many patients have "topically resistant" disease that requires a systemic (oral) approach. This 16-week randomized controlled trial is the first to directly compare two oral medications for these specific sites: roflumilast (a daily 500 mcg pill) and methotrexate (a standard weekly dose). The study's primary objective is to evaluate which treatment is more effective at clearing psoriatic lesions in the skin folds and genital area, and how each drug improves the patient's overall quality of life and symptoms like pruritus (itching). Participants are randomly assigned to one of the two treatment groups and are monitored monthly to assess skin clearance, symptom relief, and safety/tolerability. The goal of this research is to provide patients and healthcare providers with evidence-based data on a convenient, oral treatment option that does not require intensive laboratory monitoring.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Flexural Psoriasis (Also Known as Inverse or Intertriginous Psoriasis) and Genital Psoriasis

Interventions

MethotrexateDRUG

Participants in this arm receive methotrexate at a weight-based dosage of 0.2-0.4 mg/kg administered once weekly for 16 weeks. Distinguishing Details: Methotrexate serves as the established active comparator and is a cornerstone of traditional systemic psoriasis therapy. It distinguishes itself from the experimental arm through its mechanism as a non-biologic immunosuppressant, and its requirement for comprehensive baseline and periodic laboratory monitoring of liver function, kidney function, and complete blood counts to manage potential toxicities. In this study, it is used to provide a benchmark for efficacy in clearing sensitive "special sites" like skin folds and genitalia.

Roflumilast 500 Mcg Oral TabletDRUG

Participants in this arm receive oral roflumilast at a fixed dose of 500 mcg administered once daily for a total of 16 weeks. Distinguishing Details: While roflumilast is a selective and potent phosphodiesterase-4 (PDE-4) inhibitor, this study evaluates its off-label systemic use specifically for flexural and/or genital psoriasis that has proven resistant to topical therapy. Unlike its counterpart apremilast, the protocol for this study involves a fixed dose without an initial titration phase. Furthermore, as a systemic small molecule, it distinguishes itself from traditional therapies by its lack of requirement for intensive, ongoing laboratory blood monitoring

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients ≥ 18 years old. * Patients of both genders. * Patients with flexural and/or genital psoriasis that has been resistant to topical treatment, "No clearance or near clearance of lesions despite being compliant to treatment for 4 to 6 weeks". Exclusion Criteria: * Major systemic illness (cardiac, respiratory, renal, hepatic and gastrointestinal system). * Severe anemia, leucopenia or thrombocytopenia. * Pregnant and breastfeeding females. * Hypersensitivity /intolerance to Roflumilast or methotrexate. * Intake of systemic therapy for psoriasis within the last 3 Months. * Patients receiving any relevant topical treatment for at least 2 weeks before initiation of our study. * Erythrodermic, pustular psoriasis or psoriatic arthritis. * Patients with autoimmune diseases e.g., SLE. * Patients with solid or hematological malignancies e.g., breast cancer, leukemia, etc. * Patients on biological therapy within the last 6 months prior to recruitment.

Outcomes

Primary Outcomes

Clinical Success at flexural (I-IGA 0/1) and/or genital (sPGA-G 0/1) psoriasis

The proportion of patients achieving a score of 0 (clear) or 1 (almost clear) with at least a 2-point improvement from baseline at the specific sensitive sites. This is assessed using the Investigator's Global Assessment for Flexural Psoriasis (I-IGA) for skin folds and the static Physician's Global Assessment of Genitalia (sPGA-G) for genital involvement.

Time frame: week 16

Secondary Outcomes

Global Skin Clearance (PASI Responses)

The proportion of patients achieving clinically significant reductions in disease severity as measured by the Psoriasis Area and Severity Index (PASI), specifically the PASI 75, PASI 90, and PASI 100 benchmarks (representing ≥75%, ≥90%, and 100% improvement from baseline, respectively)

Time frame: Week 16

Quality of Life Improvement (DLQI 0/1)

The proportion of patients achieving a Dermatology Life Quality Index (DLQI) score of 0 or 1, signifying that the skin condition has no impact at all on the patient's overall quality of life.

Time frame: week 16

Itch Relief (Itch-NRS)

The proportion of patients achieving a clinically meaningful ≥4-point reduction from baseline in the Itch Numeric Rating Scale (Itch-NRS) or reaching an absolute score of 0 or 1 (no itch or minimal itch)

Time frame: week 16

Safety and Tolerability (Adverse Events)

The incidence, nature, and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs) documented in both treatment arms. This includes monitoring for dropouts specifically due to drug-related side effects.

Time frame: Throughout the 16-week treatment period and during the follow-up period (at least 3 months)

Body Surface Area (BSA) Reduction

The proportion of patients achieving an absolute Body Surface Area (BSA) involvement of ≤1% or the mean percentage change in BSA from baseline to the end of the study.

Time frame: week 16